Human onchocerciasis afflicts an estimated 40 million persons worldwide and is a major cause of blindness, yet has been studied only minimally using modern immunologic techniques. Cryopreserved nodules from Guatemalan patients will be utilized as a source for living microfilariae. Peripheral blood leukocytes from normal subjects will be fractionated over discontinuous metrizamide gradients, and purified eosinophils, lymphocytes, and neutrophils will be allowed to interact in vitro with microfilariae. The effect of immune serum and/or complement on this interaction will be studied. Further, the mechanism of action of diethylcarbamazine (DEC) will be investigated in this in vitro system. The effect of DEC on the interaction of cells and microfilariae in the presence or absence of immune serum/complement will be examined at both the light and electron microscopic level. Brugia pahangi in the Lewis rat will be used as an in vivo model for filariasis. The effect of parenteral diethylcarbamazine on circulating microfilariae and the sequestration of organisms in viscera will be quantitated. In vitro interactions with isolated Kuppfer cells and with purified populations of peripheral blood cells will be studied in the presence and absence of DEC. In vivo decomplementation using cobra venom factor will be employed to determine the role of the complement system in the action of DEC. Lymphocyte blastogenesis to microfilarial antigens and production of the lymphokine Eosinophil Stimulation Promoter (ESP) will be evaluated longitudinally. The effect of ESP on interactions between cells and microfilariae will be studied. Cell-mediated immunity in human onchocerciasis will be assessed by lymphocyte blastogenesis and lymphokine production in response to microfilarial antigens. Evidence for suppressor cell activity in chronically-infected patients will be sought. Onchocerciasis represents a useful model for immune-mediated ocular inflammatory disease in man.